Transforming Growth Factor β/Bone Morphogenic Protein Signaling in Pulmonary Arterial Hypertension: Remodeling Revisited

Growth factors of the transforming growth factor (TGF) β superfamily have emerged as important regulators of normal cardiovascular development, as well as modulators of the onset or progression of vascular diseases. Recently, familial and idiopathic pulmonary arterial hypertension (IPAH) has been causally linked to somatic and genetic perturbations to the TGF-β/bone morphogenic protein (BMP) system, particularly because heterogeneous germline mutations in bmpr2 (encoding the type II BMP receptor) have been detected in IPAH patients. Transgenic animal models and functional genomic studies have begun investigating TGF-β/BMP-induced effects in the pulmonary vasculature, as well as the cellular effects of bmpr2 mutations on vascular cell phenotypes. While these studies have significantly increased our knowledge about the biologic effects of TGF-β/BMP signaling in the lung vasculature, the molecular mechanisms leading to pulmonary vasculopathy in the context of bmpr2 mutations in IPAH remain largely unknown.